Background/Purpose:   Galectin 1 (Gal1) is a type of lectin expressed in a wide variety of tissues and organs. In the immune context, is broadly described its function as a negative regulator in different animal models of autoimmune diseases. The treatment with recombinant Gal1 has a therapeutic effect in the murine model of collagen-induced arthritis. In this work we studied the effect of genetic variants on Gal1 gene (LGALS1) over the Gal1 expression and its relationship with clinical parameters of severity in patients with early arthritis (EA).

Methods:   Princesa Early Arthritis Register Longitudinal (PEARL) study includes patients with early arthritis (EA). Demographic, clinical, laboratory, therapeutic and radiological data are collected along a 5 years follow-up (baseline, 6, 12, 24 and 60 months). Biological samples are obtained at each visit. We analyzed the genotype of 4 single nucleotide polymorphisms (SNPs) present in LGALS1 by PCR with TaqMan probes (n=540). Next, we fit several multivariate models by generalized estimating equations for repeated measures to analyze the statistical correlation between these genotypes and clinical parameters [Disease Activity Score 28 (DAS28) and treatment intensity] as well as correlation between these genotypes and IL-6, a key inducer of systemic inflammation which is associated with activity and severity of RA. IL-6 serum levels were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA) (n=190 patients with more than 2 visits). Gal1 serum levels were measured by ELISA and western blot (WB) was used to assess Gal1 expression in lymphocytes. Statistical analysis was performed using Stata 12 for Windows (StataCorp PL, College Station, USA). The effect of recombinant Gal1 over IL-6-secretion using anti-CD3/CD28-stimulated lymphocytes of healthy controls was also studied.

Results: We found that EA patients with at least one minor allele of the SNP rs9622682 had significantly lower levels of serum IL-6 (p=0.003 GA genotype and p=0.002 AA genotype). In addition, we observed that EA patients with AA genotype for rs9622682 showed higher levels of serum Gal1 and an increased expression of Gal1 on peripheral blood lymphocytes measured by WB compared to GG patients. That SNP showed partial linkage disequilibrium (LD) (R²=0.6) with the rs929039 located in the LGALS1 promoter. The presence of minor alleles of rs929039 displayed a similar effect over IL-6 and Gal1 levels than rs9622682. Different combinations of minor alleles of those SNPs could amplify the increased expression of Gal1 observed in EA patients. On the other hand, treatment of anti-CD3/CD28-stimulated lymphocytes with recombinant Gal1 reduced IL-6 in vitro expression levels in healthy donors.

Conclusion: The presence of minor alleles of SNPs of LGALS1 rs9622682 and rs929039 may affect the expression of Gal1 and this finding is associated with lower levels of IL-6 in serum of patients with EA, suggesting a potential prognostic value for these genetic variants.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/galectin-1-as-potential-prognostic-biomarker-in-rheumatoid-arthritis/